Multiple Myeloma: Symptoms, Treatment Options and New Research

Sept. 8, 2008 — Though it isn’t as well-known as other blood-related cancers, multiple myeloma is no less common, and its numbers are on the rise. Ravi Vij, MD, a medical oncologist at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, discusses symptoms, treatment options and a new effort to understand the genetics of the disease.

On this edition of Cancer Connection, we’ll talk about multiple myeloma, what the treatment outlook is for patients and emerging therapies on the horizon.

Host: Thanks for downloading this podcast from the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St Louis. I’m Jason Merrill. Multiple myeloma and other plasma cell neoplasms or cancers are diseases in which the body makes too many plasma cells. There are different types of treatment for patients with multiple myeloma that have come a long way over the past few years, and to tell us more about them is Siteman Cancer Center oncologist Ravi Vij. Dr. Vij, thank you for joining us.

Vij: It’s a pleasure to be on your show.

Host: What is multiple myeloma? Let’s just start there at the beginning.

Vij: Multiple myeloma is a cancer that arises from bone marrow cells. There are a number of different cancers that arise from the bone marrow. People are more familiar with cancers like leukemia. Myeloma arises from a slightly different bone marrow cell than leukemia does but is more prevalent than literally any kind of leukemia.

Host: While the prevalence of the disease is on the rise, it seems that those who are diagnosed are living longer. Why is that?

Vij: I think that is due to the fact that we now have better treatment options to offer these patients. A few years ago, we had little in the way of therapies to offer these patients. Then it was probably in the mid-90s that the advent of high-dose therapy and autologous stem cell transplantation provided the first major advance in longevity for patients. Over the last 10 years, we have developed much better drugs for this disease, chief among them drugs of the class of what we call immunomodulatory agents, of which two -- thalidomide and lenalidomide -- are currently on the market. Secondly, there are drugs that work through a mechanism called proteasome inhibition, which is how bortezomib, another drug that has now been on the market for several years, works. Each one of these drugs is adding to one’s survival. How well we’re doing for sure is not known because we need to have long-term follow-up data and then be able to look back and see how we are doing in the present age. But I’m pretty confident that we have added a year to two at least to an individual’s lifespan with these new agents.

Host: Typically, how does it work if someone is diagnosed with multiple myeloma? What should they know?

Vij: Well, I think that patients with multiple myeloma should first of all know what to expect from their disease and also what treatment options there are for them. In terms of what myeloma does to an individual, most patients with myeloma, when they present, have bone pain. The reason is that in patients with myeloma, the cells that become cancerous are the plasma cells in the bone marrow. These secrete substances that make calcium leach out of the bones and make them brittle and more prone to fracture. Another thing that patients with myeloma are more prone to develop is infections because the cells that give rise to myeloma, these plasma cells, usually provide immunity to the body to fight infections. And when they become cancerous, they don’t provide effective immunity. Another thing patients with myeloma experience is a decline in their blood counts. They’re often anemic when they first present, and that is simplistically speaking because if the bone marrow is full of cancer cells, there’s no place for normal cells to be produced. Patients with myeloma can also have an abnormality in the kidney function develop because proteins that these myeloma cells make do tend to clog the kidneys up. And lastly, patients with myeloma sometimes can have a rise in their blood calcium levels that leads to drowsiness and confusion.

In regards to treatment options for these patients with myeloma, we’ve come a long way. I think that there is some controversy right now as to what is the best standard-of-care treatment for myeloma, and that is a result of the proliferation of treatment options that we have now. It may take a little time for people to compare these treatments and decide which is the best treatment algorithm.

I think one of the things that has been a treatment decision-making factor at the beginning is whether a person is eligible for a stem cell transplant or not. Patients who are eligible for stem cell transplant should get treatment that does not damage our ability to collect stem cells. That is of paramount importance. Medicare will pay for transplants up to 76 years of age, and we certainly do transplants in people in their late 60s and early 70s in a lot of instances. So I think it is important for people to realize that they may perceive themselves not to be candidates for transplant, but these kinds of transplants are very safe. Even in their late 60s and early 70s, patients may have only a less than 5 percent chance of life-threatening events with these kind of transplants.

For those who are not transplant candidates, then there are some other different chemotherapy drugs that have become more standard, drugs that now have been combined with a new drug. Chiefly melphalan is the drug that patients who are not stem cell transplant candidates get in combination with other drugs, though newer drugs are being looked at in new regimens as well.

Host: Talk about some of those drugs. There are other emerging therapies you are studying at Siteman. What are they, and what role will they play in treatment in the future?

Vij: I think that of the proliferation of drugs in myeloma, what we have found is two classes of drugs -- immunomodulatory drugs and the proteasome inhibitors -- are very active. We now have new agents in these classes being studied. Some of these are proving to be, in early trials, possibly even more active than our current drugs. And then some are seeming to work even in people who fail currently available drugs. Among these classes of drugs, pomalidomide, which is a third-generation immunomodulatory drug, is being studied in phase I and II trials. Another drug from the proteasome inhibitor class, carfilzomib, is being looked at in patients with relapsed and refractory myeloma, and we have seen very encouraging results with this drug.

Host: Your team at Siteman is a member of the Multiple Myeloma Research Consortium. Talk about that organization and its goals.

Vij: The Multiple Myeloma Research Consortium is a unique enterprise that is a collaboration among, at the moment, 15 major academic centers that are thought to be the top leaders in multiple myeloma, the pharmaceutical industry and also companies that are coming up in the biotechnology field. The goal is to validate new compounds being generated and then to move these drugs rapidly into what we call phase I dose-finding and subsequently phase II trials to assess efficacy. It is hoped that with the large number of premier medical centers in this consortium, it will accelerate drug development, and more promising drugs will move forth more quickly from the bench to the bedside.

Host: Recently you received an anonymous gift you’ll be using to identify genetic mutations for multiple myeloma. What do you hope to find?

Vij: We are very grateful to the individual who has given us a fairly sizable grant to work toward deciphering some of the secrets of myeloma. We’re going to be using this, in addition to genetic mutations, to also develop the ability to study novel compounds in the laboratory and hope that we could then move these into clinical trials.

In regards to the specific question of genetic mutations, we are one of the three centers in the world that can do high-output gene sequencing studies. The Human Genome Project that led to the deciphering of the human genome, the federal effort was led at three institutions. There was the Broad Institute at Harvard, the Sanger Institute in England and here at Washington University. It took several years to sequence the genome of a single individual. Now several human genomes can be sequenced in just a few months, and the cost of this technology has also gone down dramatically. So we hope to be able to use our unique position in high-output gene sequencing to identify candidate genes that could lead to the development of myeloma in individuals and also hopefully give us targets to develop new drugs against.

Host: Dr. Vij, thanks for joining us.

Vij: It’s a pleasure.

Host: For more information about multiple myeloma, you can visit the Siteman Cancer Center online at www.siteman.wustl.edu or call 800-600-3606. Thanks for downloading. Until next time, I’m Jason Merrill.